Interaction of 2,3,7,8-tetrachlorodibenzo-p-dioxin, 12-O-tetradecanoylphorbol-13-acetate (TPA) and 17β-estradiol in MCF-7 human breast cancer cells

M. Moore, T. R. Narasimhan, X. Wang, V. Krishnan, S. Safe, H. J. Williams, A. I. Scott

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 12-O-tetradecanoylphorbol-13-acetate (TPA) are both tumor promoters which act through different mechanisms. In MCF-7 human breast cancer cells both TCDD and TPA inhibited constitutive and 17β-estradiol-induced cell proliferation but showed no apparent interactive effects. TCDD also inhibited the 17β-estradiol-induced secretion of the 52-kDa protein (procathepsin D) and induced CYP1A1 gene expression whereas TPA alone was inactive for these responses. Moreover, TPA did not modulate the TCDD-mediated antiestrogenic or induction responses and did not decrease levels of the nuclear Ah receptor complex as determined in a gel mobility shift assay using a 32P-dioxin responsive element (DRE). The interactions of TPA and TCDD on the metabolism of [13C]glucose to [13C]lactate was also investigated using 13C-nuclear magnetic resonance spectroscopy. The rate of formation of [13C]lactate in M [13C]glucose in MCF-7 cells treated with DMSO (control), 1 nM 17β-estradiol, 1 nM TCDD, 1 nM TCDD plus 1 nM 17β-estradiol, and 0.1 ng/ml TPA plus 1 nM 17β-estradiol was 28, 48, 20, 22 and 50 fmol lactate formed/cell/h, respectively. Thus, TCDD, but not TPA, inhibited this estrogen-induced response. However, a comparison of the rate of lactate formation in cells treated with TCDD plus 17β-estradiol (22 fmol/cell/h) or TCDD plus 17β-estradiol plus TPA (61 fmol/cell/h) showed that TPA significantly inhibited the TCDD-mediated antiestrogenic response. The results of these studies in MCF-7 cells demonstrate that the interactions of TCDD and TPA are highly response-specific and do not involve TPA-mediated downregulation of the nuclear Ah receptor complex.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume44
Issue number3
DOIs
StatePublished - Mar 1993
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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